MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in th...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0194911X_v70_n5_p982_Cerniello http://hdl.handle.net/20.500.12110/paper_0194911X_v70_n5_p982_Cerniello |
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paper:paper_0194911X_v70_n5_p982_Cerniello2023-06-08T15:20:06Z MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway angiotensin-(1-7) arrestin endocytosis endosomes MAS1 receptor trafficking angiotensin[1-7] beta arrestin 2 caveolin 1 dynamin G protein coupled receptor MAS1 receptor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein kinase B Rab protein Rab11 protein short hairpin RNA unclassified drug yellow fluorescent protein angiotensin I angiotensin I (1-7) beta arrestin 2 G protein coupled receptor mitogen activated protein kinase oncoprotein peptide fragment proto-oncogene proteins c-mas-1 Article cell membrane controlled study embryo endosome enzyme activation genetic transfection HEK293T cell line human human cell internalization lysosome priority journal receptor binding assay endocytosis HEK293 cell line metabolism physiology protein transport signal transduction Angiotensin I beta-Arrestin 2 Endocytosis Endosomes Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Protein Transport Proto-Oncogene Proteins Receptors, G-Protein-Coupled Signal Transduction The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell. © 2017 American Heart Association, Inc. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0194911X_v70_n5_p982_Cerniello http://hdl.handle.net/20.500.12110/paper_0194911X_v70_n5_p982_Cerniello |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
angiotensin-(1-7) arrestin endocytosis endosomes MAS1 receptor trafficking angiotensin[1-7] beta arrestin 2 caveolin 1 dynamin G protein coupled receptor MAS1 receptor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein kinase B Rab protein Rab11 protein short hairpin RNA unclassified drug yellow fluorescent protein angiotensin I angiotensin I (1-7) beta arrestin 2 G protein coupled receptor mitogen activated protein kinase oncoprotein peptide fragment proto-oncogene proteins c-mas-1 Article cell membrane controlled study embryo endosome enzyme activation genetic transfection HEK293T cell line human human cell internalization lysosome priority journal receptor binding assay endocytosis HEK293 cell line metabolism physiology protein transport signal transduction Angiotensin I beta-Arrestin 2 Endocytosis Endosomes Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Protein Transport Proto-Oncogene Proteins Receptors, G-Protein-Coupled Signal Transduction |
| spellingShingle |
angiotensin-(1-7) arrestin endocytosis endosomes MAS1 receptor trafficking angiotensin[1-7] beta arrestin 2 caveolin 1 dynamin G protein coupled receptor MAS1 receptor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein kinase B Rab protein Rab11 protein short hairpin RNA unclassified drug yellow fluorescent protein angiotensin I angiotensin I (1-7) beta arrestin 2 G protein coupled receptor mitogen activated protein kinase oncoprotein peptide fragment proto-oncogene proteins c-mas-1 Article cell membrane controlled study embryo endosome enzyme activation genetic transfection HEK293T cell line human human cell internalization lysosome priority journal receptor binding assay endocytosis HEK293 cell line metabolism physiology protein transport signal transduction Angiotensin I beta-Arrestin 2 Endocytosis Endosomes Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Protein Transport Proto-Oncogene Proteins Receptors, G-Protein-Coupled Signal Transduction MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| topic_facet |
angiotensin-(1-7) arrestin endocytosis endosomes MAS1 receptor trafficking angiotensin[1-7] beta arrestin 2 caveolin 1 dynamin G protein coupled receptor MAS1 receptor mitogen activated protein kinase 1 mitogen activated protein kinase 3 protein kinase B Rab protein Rab11 protein short hairpin RNA unclassified drug yellow fluorescent protein angiotensin I angiotensin I (1-7) beta arrestin 2 G protein coupled receptor mitogen activated protein kinase oncoprotein peptide fragment proto-oncogene proteins c-mas-1 Article cell membrane controlled study embryo endosome enzyme activation genetic transfection HEK293T cell line human human cell internalization lysosome priority journal receptor binding assay endocytosis HEK293 cell line metabolism physiology protein transport signal transduction Angiotensin I beta-Arrestin 2 Endocytosis Endosomes Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Protein Transport Proto-Oncogene Proteins Receptors, G-Protein-Coupled Signal Transduction |
| description |
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein). MAS1R internalization was evaluated by measuring the MAS1R present in the plasma membrane after agonist stimulation using a ligand-binding assay. MAS1R trafficking was evaluated by its colocalization with trafficking markers. MAS1R internalization was blocked in the presence of shRNAcaveolin-1 and with dominant negatives for Eps15 (a protein involved in endocytosed Rs by clathrin-coated pits) and for dynamin. After stimulation, MAS1R colocalized with Rab11 - a slow recycling vesicle marker - and not with Rab4 - a fast recycling vesicle marker - or LysoTracker - a lysosome marker. Cells transfected with MAS1R showed an increase in Akt and ERK1/2 activation on angiotensin-(1-7) stimulation, which was blocked when the clathrin-coated pits pathway was blocked. Suppression of β-arrestin2 by shRNA reduced the angiotensin-(1-7)-induced ERK1/2 activation, whereas Akt activation was not modified. We conclude that on agonist stimulation, MAS1R is internalized through clathrin-coated pits and caveolae in a dynamin-dependent manner and is then slowly recycled back to the plasma membrane. MAS1R induced Akt and ERK1/2 activation from early endosomes, and the activation of ERK1/2 was mediated by β-arrestin2. Thus, MAS1R activity and density may be tightly controlled by the cell. © 2017 American Heart Association, Inc. |
| title |
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| title_short |
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| title_full |
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| title_fullStr |
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| title_full_unstemmed |
MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway |
| title_sort |
mas1 receptor trafficking involves erk1/2 activation through a β-arrestin2-dependent pathway |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0194911X_v70_n5_p982_Cerniello http://hdl.handle.net/20.500.12110/paper_0194911X_v70_n5_p982_Cerniello |
| _version_ |
1768542501663145984 |